Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	GOG-9202

Objectives

I.  Determine the maximum tolerated dose (MTD) of paclitaxel (Taxol) and 
carboplatin (TAX/CBDCA) with granulocyte colony stimulating factor in patients 
with untreated Stage III/IV ovarian epithelial or primary peritoneal cancer.

II.  Define further the pharmacokinetics of TAX in patients with untreated 
ovarian epithelial or primary peritoneal cancer.

III.  Determine the effect of TAX upon the pharmacokinetics and toxicity of 
CBDCA.

IV.  Define the mechanism of cytotoxicity of TAX by examining its effects on 
human ovarian or peritoneal cancer cells.

V.  Define an MTD based on thrombocytopenia, and evaluate interleukin-6 impact 
on thrombocytopenia, dose intensity, and cumulative dose delivery.

Entry Criteria

Disease Characteristics:

Histologically confirmed, previously untreated, Stage III/IV primary
peritoneal or ovarian epithelial cancer of the following types:
  Serous adenocarcinoma        Endometrioid adenocarcinoma
  Mucinous adenocarcinoma      Undifferentiated carcinoma
  Clear cell adenocarcinoma    Mixed epithelial carcinoma

No borderline carcinoma or "probably malignant" tumors

No unclassified ovarian cancer

Measurable or nonmeasurable disease allowed
  Cytologic confirmation required if entry is based on malignant pleural
  effusion

Prior/Concurrent Therapy:

Biologic therapy:
  No prior biologic therapy

Chemotherapy:
  No prior cancer chemotherapy

Endocrine therapy:
  No prior endocrine therapy

Radiotherapy:
  No prior radiotherapy to abdomen or pelvis

Surgery:
  Optimum surgery required (including total abdominal hysterectomy with
  bilateral salpingo-oophorectomy, if appropriate

Patient Characteristics:

Age:
  18 and over

Performance status:
  GOG 0-2

Hematopoietic:
  WBC at least 4,000
  Platelets at least 100,000

Hepatic:
  Bilirubin no more than 1.5 x normal
  SGOT no more than 3 x normal
  No acute hepatitis

Renal:
  Creatinine no more than 1.5 mg/dl

Cardiovascular:
  No history of CHF
  No unstable angina
  No MI within 6 months
  No abnormal cardiac conduction (e.g., bundle branch block, A-V block) unless
     stable for 6 months
  No concurrent use of medications that may affect cardiac conduction,
  including:
     Digoxin
     Propranolol
     Calcium channel blockers

Other:
  No septicemia or severe infection
  No severe GI bleeding
  Negative pregnancy test required of fertile patients
  Effective contraception required of fertile patients

  In patients receiving interleukin-6:
     No lymphoproliferative disorder
     No abnormal paraprotein on serum protein electrophoresis
     No HIV infection
     No autoimmune disease
     No chronic glomerulonephritis

Expected Enrollment

At least 3 patients will be entered for each dose studied.  First, an MTD was 
determined for CBDCA with a 24-hour infusion of TAX (MTD = a target AUC of 
7.5).  Second, an MTD was defined for TAX with CBDCA at the MTD and with G-CSF 
(MTD = 175 mg/sqm).  Third, a new MTD was defined for a 3-hour infusion of TAX 
with CBDCA with and without G-CSF (MTD = 175 mg/sqm).  Fourth, a new MTD based 
on thrombocytopenia was defined for CBDCA with TAX/G-CSF (MTD = CBDCA at a 
target AUC of 10).  As of July 1995, the ability of IL-6 to protect against 
thrombocytopenia is being evaluated with CBDCA at a target AUC of 12.  As of 
November 1995, 3 additional patients will be treated at the CBDCA dose of a 
target AUC of 10 (for a total of 6 patients); the study will then close.

Outline

2-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation.  
Paclitaxel, Taxol, TAX, NSC-125973; Carboplatin, CBDCA, NSC-241240; with 
Granulocyte Colony Stimulating Factor (Amgen), G-CSF, NSC-614629; with and 
without Interleukin-6 (Sandoz), IL-6, NSC-643497.

Bookman MA, McGuire WP, Kilpatrick D, et al.: Phase-I Gynecologic Oncology Group (GOG) study of 3-hr and 24-hr paclitaxel with carboplatin as initial therapy for advanced epithelial ovarian cancer (OvCa). [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-755, 271, 1995.

Bookman MA, McGuire WP 3rd, Kilpatrick D, et al.: Carboplatin and paclitaxel in ovarian carcinoma: a phase I study of the Gynecologic Oncology Group. J Clin Oncol 14 (6): 1895-902, 1996.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Gynecologic Oncology Group

Michael Bookman, MD, Protocol chair		Ph: 215-728-2987; 888-369-2427 Email: ma_bookman@fccc.edu